Individuals with postural orthostatic tachycardia syndrome (POTS) experience many barriers that lead to decreased functioning and quality of life. At this time, there are limited resources regarding the functional impact of POTS on occupational performance. Therefore, this narrative review demonstrates how occupational therapy practitioners can conceptualize, categorize, and systematically organize their thinking around barriers individuals with POTS experience using the Person-Environment-Occupation-Performance (PEOP) model of practice.

Postural tachycardia syndrome (POTS) is a condition of orthostatic intolerance which often leads to significant functional deficits. This study explores narrative responses from a large cohort (n = 958) of individuals with POTS in describing daily life challenges and the use of strategies to manage these difficulties. Data was coded and emergent themes provided insight into daily life experiences including successful interventions and a wealth of gaps in treatment that remain unaddressed. This led to the development of clinical recommendations for occupational therapy treatment of individuals with POTS. Further research is indicated including clinical trials to demonstrate the efficacy of occupational therapy intervention.

Postural orthostatic tachycardia syndrome (POTS) is a form of dysautonomia that's characterised by an abnormal heart rate response to a positional change. A 50-year-old female presented with lightheadedness, palpitation, and neck pain for 3 years. Lightheadedness and palpitation occurred when shifting from a prolonged seated or lying position. Standing radiographs showed spinal misalignment with cervical kyphosis and thoracic scoliosis. Continuous static stress on these minor variants could aggravate biomechanical and autonomic disorder like POTS. After ruling out cardiovascular, neurological, or vestibular pathophysiology, a multicomponent treatment approach was adopted including the use of thermal ultrasound therapy, cervical and thoracic spinal manipulation, and intermittent motorized cervicothoracic traction to manage her neck pain complaints. Following 3 months of regular treatment, the patient reported a full resolution of neck pain, dizziness, and POTS. At 12-month follow-up, all radiographic metrics showed improvement, including improvement of cervical alignment and thoracic curvature. POTS is a prevalent, under-diagnosed dysautonomia. This study might arouse the alertness of clinicians that symptoms related to POTS may be erroneously attributed to other neuro-cardiovascular disorders.

Narcolepsy is a clinical syndrome of hypothalamic disorder characterized by several sleep-wake disorders. The most common features include daytime sleepiness associated with hallucinations (hypnagogic and hypnopompic hallucinations) at the transition time of sleep-wake time, cataplexy or sudden loss of muscle tone, and sleep paralysis. We present a case of a patient affected with both narcolepsy and postural orthostatic tachycardia syndrome (POTS). POTS is a rare disorder characterized by orthostatic intolerance and abnormal autonomic response while sustaining an upright posture. In this case report, we highlight the impact of POTS on the choice of pharmacotherapy for narcolepsy.

Multiple endocrine neoplasia type 2B is a genetic disorder characterized by pheochromocytoma, medullary thyroid carcinoma, and marfanoid features. Although hypertension and stress cardiomyopathy are known cardiovascular complications of pheochromocytoma, clinical presentation maybe subtle. Elevation in heart rate and lightheadedness induced by catecholamine excess may mimic clinical features of postural orthostatic tachycardia syndrome, as shown in our case report. ().

Athletic underperformance is characterized by fatigue and an inability to sustain a consistent exercise workload. We describe five elite swimmers with prolonged fatigue and athletic underperformance. Based on our work in myalgic encephalomyelitis /chronic fatigue syndrome, we focused on orthostatic intolerance as a possible contributor to symptoms. Participants were referred for evaluation of fatigue and underperformance to the Chronic Fatigue Clinic at the Johns Hopkins Children's Center. All patients were evaluated for overtraining syndrome, as well as for features commonly seen in myalgic encephalomyelitis/chronic fatigue syndrome. The latter included joint hypermobility, orthostatic intolerance, and non-IgE mediated milk protein intolerance. Orthostatic intolerance was tested by performing a ten-minute passive standing test or a head-up tilt table test. Orthostatic testing provoked fatigue and other symptoms in all five swimmers, two of whom met heart rate criteria for postural tachycardia syndrome. Treatment was individualized, primarily consisting of an increased intake of sodium chloride and fluids to address orthostasis. All patients experienced a relatively prompt improvement in fatigue and other orthostatic symptoms and were able to either return to their expected level of performance or improve their practice consistency. Orthostatic intolerance was an easily measured and treatable contributor to athletic underperformance in the five elite swimmers we describe. We suggest that passive standing tests or formal tilt table tests be incorporated into the clinical evaluation of athletes with fatigue and underperformance as well as into scientific studies of this topic. Recognition and treatment of orthostatic intolerance provides a new avenue for improving outcomes in underperforming athletes.

Patients with post-COVID-19 syndrome have reported a wide array of symptoms that include autonomic dysfunction. It is hypothesized that this may be secondary to interruption of baroreflex pathways in the carotid arteries or nucleus tractus solitarius, however, confirming studies have yet to be performed. A limited number of studies have highlighted the presence of an exaggerated baroreflex response in patients with a post-COVID-19 syndrome that mirror other chronic autonomic dysfunction-related conditions.

Patients with postural orthostatic tachycardia syndrome (POTS) experience an excessive increase in heart rate (HR) and low-frequency (∼0.1 Hz) blood pressure (BP) and HR oscillations upon head-up tilt (HUT). These responses are attributed to increased baroreflex (BR) responses modulating sympathetic and parasympathetic signalling. This study uses a closed-loop cardiovascular compartment model controlled by the BR to predict BP and HR dynamics in response to HUT. The cardiovascular model predicts these quantities in the left ventricle, upper and lower body arteries and veins. HUT is simulated by letting gravity shift blood volume (BV) from the upper to the lower body compartments, and the BR control is modelled using set-point functions modulating peripheral vascular resistance, compliance, and cardiac contractility in response to changes in mean carotid BP. We demonstrate that modulation of parameters characterizing BR sensitivity allows us to predict the persistent increase in HR and the low-frequency BP and HR oscillations observed in POTS patients. Moreover, by increasing BR sensitivity, inhibiting BR control of the lower body vasculature, and decreasing central BV, we demonstrate that it is possible to simulate patients with neuropathic and hyperadrenergic POTS.

Dizziness is a common concern discussed at adolescent medical visits. In this series, we describe 9 pediatric patients with postacute sequelae of severe acute respiratory syndrome coronavirus disease 2 (SARS-CoV-2) who presented with persistent, debilitating dizziness for weeks to months after their acute infection. Among the 9 patients, median age was 14 years (range: 11 to 17), 6 were female, and 8 had not received any SARS-CoV-2 vaccines. Five patients met diagnostic criteria for postural orthostatic tachycardia syndrome (POTS) by active standing testing and benefited from a combination of nonpharmacologic therapy (NPT) and medication. NPT alone did not improve symptoms in any patients. Patients who did not meet conventional criteria for POTS, but continued to have symptoms despite NPT compliance, also demonstrated subjective improvement in dizziness when medications were initiated. The majority of patients experienced improvement in dizziness and quality of life, including returning to sports teams and a regular school schedule. A review of the postacute sequelae of SARS-CoV-2 literature demonstrates increasing recognition of a subset of patients who develop autonomic dysfunction, including POTS, although the etiology and prognosis are not completely understood. Our case series aims to highlight the phenomenon of dysautonomia after acute SARS-CoV-2 infection and its response to therapy.

To outline a consensus-designed process for triaging and managing patients with post-coronavirus disease (COVID-19) syndrome at Mayo Clinic. We convened a central multidisciplinary team including members from the departments of general internal medicine, occupational medicine, physical medicine and rehabilitation, psychology, allergy and immunology, infectious disease, pulmonology, neurology, cardiology, and pediatrics and otorhinolaryngology with membership from all Mayo Clinic sites in Arizona, Florida, Iowa, Minnesota, and Wisconsin. Consensus recommendations were made for the best practice guidelines on triaging and managing patients. Several innovations were agreed upon, including a postacute sequelae of COVID-19-specific appointment request form for data collection, a bioregistry, a biorepository, and a postacute sequelae of COVID-19-specific treatment program. Given that each clinical site had individual clinical practices, these recommendations were implemented using different models, which may provide broad applicability to other clinical settings.

To assess the prevalence and clinical implications of persistent or exertional cardiopulmonary symptoms in young competitive athletes following SARS-CoV-2 infection. This observational cohort study from the Outcomes Registry for Cardiac Conditions in Athletes included 3597 US collegiate athletes after SARS-CoV-2 infection. Clinical characteristics, advanced diagnostic testing and SARS-CoV-2-associated sequelae were compared between athletes with persistent symptoms >3 weeks, exertional symptoms on return to exercise and those without persistent or exertional symptoms. Among 3597 athletes (mean age 20 years (SD, 1 year), 34% female), data on persistent and exertional symptoms were reported in 3529 and 3393 athletes, respectively. Persistent symptoms >3 weeks were present in 44/3529 (1.2%) athletes with 2/3529 (0.06%) reporting symptoms >12 weeks. Exertional cardiopulmonary symptoms were present in 137/3393 (4.0%) athletes. Clinical evaluation and diagnostic testing led to the diagnosis of SARS-CoV-2-associated sequelae in 12/137 (8.8%) athletes with exertional symptoms (five cardiac involvement, two pneumonia, two inappropriate sinus tachycardia, two postural orthostatic tachycardia syndrome and one pleural effusion). No SARS-CoV-2-associated sequelae were identified in athletes with isolated persistent symptoms. Of athletes with chest pain on return to exercise who underwent cardiac MRI (CMR), 5/24 (20.8%) had probable or definite cardiac involvement. In contrast, no athlete with exertional symptoms without chest pain who underwent CMR (0/20) was diagnosed with probable or definite SARS-CoV-2 cardiac involvement. Collegiate athletes with SARS-CoV-2 infection have a low prevalence of persistent or exertional symptoms on return to exercise. Exertional cardiopulmonary symptoms, specifically chest pain, warrant a comprehensive evaluation.

Postural orthostatic tachycardia syndrome (POTS) is a disorder of orthostatic intolerance that primarily affects women of childbearing age. The underlying pathophysiology of POTS is not fully understood, but it has been suggested that autoimmunity may play a role. The aim of this study was to compare concentrations of autoantibodies to cardiovascular G protein-coupled receptors between patients with POTS and healthy controls. Sera were collected from 116 patients with POTS (91% female; medium age, 29 years) and 81 healthy controls (84% female; medium age, 27 years) from Calgary, Canada, and Malmö, Sweden. Samples were evaluated for autoantibodies to 11 receptors (adrenergic, muscarinic, angiotensin II, and endothelin) using a commercially available enzyme-linked immunosorbent assay. Autoantibody concentrations against all of the receptors tested were not significantly different between controls and patients with POTS. The majority of patients with POTS (98.3%) and all controls (100%) had α1 adrenergic receptor autoantibody concentrations above the seropositive threshold provided by the manufacturer (7 units/mL). The proportion of patients with POTS versus healthy controls who fell above the diagnostic thresholds was not different for any tested autoantibodies. Receiver operating characteristic curves showed a poor ability to discriminate between patients with POTS and controls. Patients with POTS and healthy controls do not differ in their enzyme-linked immunosorbent assay-derived autoantibody concentrations to cardiovascular G protein-coupled receptors. These findings suggest that these tests are not useful for establishing the role of autoimmunity in POTS.

Sinus tachycardia (ST) is ubiquitous, but its presence outside of normal physiological triggers in otherwise healthy individuals remains a commonly encountered phenomenon in medical practice. In many cases, ST can be readily explained by a current medical condition that precipitates an increase in the sinus rate, but ST at rest without physiological triggers may also represent a spectrum of normal. In other cases, ST may not have an easily explainable cause but may represent serious underlying pathology and can be associated with intolerable symptoms. The classification of ST, consideration of possible etiologies, as well as the decisions of when and how to intervene can be difficult. ST can be classified as secondary to a specific, usually treatable, medical condition (eg, pulmonary embolism, anemia, infection, or hyperthyroidism) or be related to several incompletely defined conditions (eg, inappropriate ST, postural tachycardia syndrome, mast cell disorder, or post-COVID syndrome). While cardiologists and cardiac electrophysiologists often evaluate patients with symptoms associated with persistent or paroxysmal ST, an optimal approach remains uncertain. Due to the many possible conditions associated with ST, and an overlap in medical specialists who see these patients, the inclusion of experts in different fields is essential for a more comprehensive understanding. This article is unique in that it was composed by international experts in Neurology, Psychology, Autonomic Medicine, Allergy and Immunology, Exercise Physiology, Pulmonology and Critical Care Medicine, Endocrinology, Cardiology, and Cardiac Electrophysiology in the hope that it will facilitate a more complete understanding and thereby result in the better care of patients with ST.

Patients with pelvic congestion syndrome (PCS) often report overlapping somatic symptoms and syndromes. The objective of this study was to explore the prevalence of co-existing symptoms and self-reported syndrome diagnoses among women with PCS and to inform future research hypotheses. A brief online survey was offered to members of a PCS support group website. Responses were assessed for self-reported co-existing symptoms and formal diagnoses, including: chronic fatigue syndrome, fibromyalgia, postural tachycardia syndrome, irritable bowel syndrome, migraines, interstitial cystitis, and temporomandibular joint dysfunction. Of a total of 6000 members, there were 398 respondents; 232 (59%) had not yet been treated for PCS. Among these, the most prevalent co-existing symptoms were as follows: severe fatigue (72%), dizziness (63%), IBS symptoms (61%), brain fog (33%), migraines (49%), polyuria or dysuria (41%), excessive sweating (31%), TMJ pain (31%), and loose skin or lax joints (18%). These are much higher than reported for the general female population. The most commonly self-reported comorbid syndrome diagnoses for the overall group of 398 were: irritable bowel syndrome (29%), fibromyalgia (13%), spinal nerve problems (18%), interstitial cystitis (10%), postural tachycardia syndrome (9%), hypertension (11%), chronic fatigue syndrome (10%), and Ehlers-Danlos syndrome (6%). Other than with hypertension, these rates are variably higher than in the general population. Several self-reported co-existing symptoms and syndromes are more prevalent in members of a PCS support group relative to the reported prevalence in the general population. More formal investigation is warranted to evaluate this finding and to investigate potential etiologic links. Ehlers-Danlos Syndrome appears to be common in self identifying PCS women.

The association between dysautonomia and long-COVID syndrome has gained considerable interest. This study retrospectively characterized the findings of autonomic reflex screen (ARS) in long-COVID patients presenting with orthostatic intolerance (OI). Fourteen patients were identified. All patients had normal cardiovagal function and 2 patients had abnormal sudomotor function. The head-up tilt table (HUTT) was significantly abnormal in 3 patients showing postural orthostatic tachycardia syndrome (POTS). CASS ranged from 0 to 2. The most common clinical scenario was symptoms of orthostatic intolerance without demonstrable HUTT orthostatic tachycardia or orthostatic hypotension (OH) (n = 8, 57 %). In our case series, most long-COVID patients presenting to our laboratory with OI had no significant HUTT abnormalities; only 3 patients met the criteria for POTS.

Orthostatic hypotension (OH) commonly affects the elderly and can be challenging to manage. Its symptomology can be variable and is induced by decreased cerebral perfusion. Here, we present a complex yet compelling case of a patient with refractory OH, focusing on delineating current medical therapies and pathophysiology for in-training medical professionals.

The COVID-19 pandemic has dramatically affected societies and healthcare systems around the globe. The perioperative care continuum has also been under significant strain due to the pandemic-tasked with simultaneously addressing surgical strains and backlogs, infection prevention strategies, and emerging data regarding significantly higher perioperative risk for COVID-19 patients and survivors. Many uncertainties persist regarding the perioperative risk, assessment, and management of COVID-19 survivors-and the energy to catch up on surgical backlogs must be tempered with strategies to continue to mitigate COVID-19 related perioperative risk. Here, we review the available data for COVID-19-related perioperative risk, discuss areas of persistent uncertainty, and empower the perioperative teams to pursue evidence-based strategies for high quality, patient-centered, team-based care as we enter the third year of the COVID-19 pandemic.

Background Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder affecting multiple systems, particularly the cardiovascular system. The leading causes of death in MFS are aortopathies and valvular disease. We wanted to identify the frequency of arrhythmia and postural orthostatic tachycardia syndrome, length of hospital stay, health care-associated costs (HAC), and in-hospital mortality in patients with MFS. Methods and Results The National Inpatient Sample database from 2005 to 2014 was queried using () codes for MFS and arrhythmias. Patients were classified into subgroups: supraventricular tachycardia, ventricular tachycardia (VT), atrial fibrillation, atrial flutter, and without any type of arrhythmia. Data about length of stay, HAC, and in-hospital mortality were also abstracted from National Inpatient Sample database. Adjusted HAC was calculated as multiplying HAC and cost-to-charge ratio; 12 079 MFS hospitalizations were identified; 1893 patients (15.7%) had an arrhythmia; and 4.9% of the patients had postural orthostatic tachycardia syndrome. Median values of length of stay and adjusted HAC in VT group were the highest among the groups (VT: 6 days, $18 975.8; supraventricular tachycardia: 4 days, $11 906.6; atrial flutter: 4 days, $11 274.5; atrial fibrillation: 5 days, $10431.4; without any type of arrhythmia: 4 days, $8336.6; both =0.0001). VT group had highest in-patient mortality (VT: 5.3%, atrial fibrillation: 4.1%, without any type of arrhythmia: 2.1%, atrial flutter: 1.7%, supraventricular tachycardia: 0%; <0.0001) even after adjustment for potential confounders (without any type of arrhythmia versus VT; odds ratio [95% CI]: 3.18 [1.62-6.24], =0.001). Conclusions Arrhythmias and postural orthostatic tachycardia syndrome in MFS were high and associated with increased length of stay, HAC, and in-hospital mortality especially in patients with VT.

Post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (PASC) infection is particularly concerning to athletes who place a high premium on cardiovascular performance and competition. This initial case series shows the overlap between PASC and orthostatic intolerance in athletes, reveals the diagnostic challenges, and highlights the role of graded exercise training in this population. ().

Postural orthostatic tachycardia syndrome (POTS) is an increasingly well-recognized condition encountered in clinical practice. Diagnosis and treatment remain extremely challenging. The limited success of currently available therapies has laid the foundation for a number of experimental therapies. In this review, we will briefly outline the pathophysiology and clinical features of this syndrome, before moving on to its management, with a specific focus on experimental pharmacological therapies. Finally, we briefly discuss POTS related to the SARS CoV-2 (COVID-19) pandemic. Despite tremendous advances, the diagnosis and management of POTS remains extremely challenging. The multitude of contributory mechanisms, which predominate to varying degrees in different patients further complicates management. Improved characterization of pathophysiological phenotypes is essential to individualize management. Lifestyle measures form the first line of therapy, followed by beta-blockers, ivabradine, fludrocortisone, and midodrine. Supplemental therapies such as iron, vitamin D and α lipoic acid are quite safe and a trial of their use is reasonable. The use of erythropoietin, IVIG, desmopressin, etc., are more specialized and nuanced alternatives. In recent years, interest has grown in the use of cardiac neuromodulation. Though preliminary, some of these therapies are quite promising.

We explore the anatomy of the central and peripheral autonomic pathways involved in primary headache as well as the mechanisms for secondary headache associated with disorders of the autonomic nervous system. The prevalence and clinical presentation of cranial and systemic autonomic symptoms in these conditions will be discussed, with a focus on recent studies. Several small studies have utilized the relationship between headache and the autonomic nervous system to identify potential biomarkers to aid in diagnosis of migraine and cluster headache. Headache in postural orthostatic tachycardia syndrome (POTS) has also been further characterized, particularly in its association with orthostatic headache and spontaneous intracranial hypotension (SIH). This review examines the pathophysiology of primary and secondary headache disorders in the context of the autonomic nervous system. Mechanisms of headache associated with systemic autonomic disorders are also reviewed.

Headache is a common presentation of postural tachycardia syndrome, yet robust prevalence data is lacking. To undertake a systematic review and meta-analysis to estimate the prevalence of headache disorders in postural tachycardia syndrome, and to explore the potential shared pathophysiological mechanisms that underpin these conditions as well as treatment options. Three databases were searched for publications evaluating prevalence of migraine (primary outcome) and general and orthostatic headache (secondary outcomes) in patients with postural tachycardia syndrome. Two independent reviewers selected studies and extracted data. A random-effects meta-analysis calculated the pooled prevalence of migraine in postural tachycardia syndrome. A narrative literature review explored the pathophysiology and treatment options for concurrent headache disorders and postural tachycardia syndrome. Twenty-three articles met inclusion criteria. Estimated pooled prevalence of migraine in postural tachycardia syndrome was 36.8% (95% CI 2.9-70.7%). Various shared pathophysiological pathways for these conditions, as well as proposed treatment strategies, were identified.: Heterogeneity of study design, populations, and methodology for identifying headache disorders and postural tachycardia syndrome limited the generalisability of results. Migraine is a commonly reported comorbidity in POTS, however the true prevalence cannot be determined from the current literature. Further studies are required to assess this comorbidity and investigate the underlying mechanisms, as well as identify effective treatment strategies.

Introduction Postural orthostatic tachycardia syndrome (POTS) is an underdiagnosed and undertreated dysautonomia. We hypothesize that there are differences between primary care physicians (PCPs) and patients' perceptions of POTS and that correcting these discrepancies may improve patient care.  Methods Two groups were surveyed: Patients who received care for POTS symptoms from a Cleveland Clinic neurologist or nurse practitioner and patients who received care from Cleveland Clinic family medicine or internal medicine physicians.  Results PCPs (81%) rated lightheadedness as the symptom with the most significant negative impact on patient's quality of life with POTS, while patients rated fatigue (32%) as their worst symptom. PCPs were somewhat comfortable managing POTS but were less confident recommending cardiac rehabilitation and daily behavioral measures.  Conclusion PCPs may need to continue review the negative impact of fatigue on the quality of life of POTS patients as well symptoms of body pain and lightheadedness. Although they are relatively comfortable managing POTS, PCPs may benefit from training on several aspects of POTS treatment.

Orthostatic intolerance (OI) following pediatric concussion is not well understood. Assessing the prevalence of concussion-related OI and how it compares to non-concussion-related OI will improve care for patients suffering with these symptoms. OBJECTIVE: We set out to describe concussion-related OI in adolescence, with particular emphasis on time to recovery and differences from non-concussion-related OI (including male vs. female prevalence). Retrospective chart reviews were completed on post-concussion patients endorsing symptoms of OI. The patients' sex, sport history, previous concussions, time since injury, and recovery time were analyzed and compared between males and females as well as against general OI statistics. Thirty-nine pediatric patients, representing 8.7% of all new patients referred to a specialized concussion clinic over a 13-month interval, were included in the chart review. Mean age of onset was 15.0 ± 2.5 years and 18 (46%) were males. The median times from evaluation to symptom resolution were 120 days. Of 18 patients who completed head-up tilt table testing, 17 (94%) had orthostatic tachycardic response (>40 bpm heart rate increment). Post-concussive OI differs from other orthostatic intolerance etiologies, lacking a strong female predominance and exhibiting a shorter time course to recovery compared to other etiologies of OI (but longer recovery time compared to concussion patients in general). Clinical orthostatic vital signs may not be sensitive for diagnosing orthostatic intolerance in athletes, likely due to higher vagal tone and more efficient skeletal muscle pump.

Long-term health problems such as fatigue, palpitations, syncope, and dizziness are well-known in patients after COVID-19 (post-acute sequelae of coronavirus (PASC)). More recently, comparable problems have been noticed after the SARS-CoV-2 vaccination (post-VAC). The pathophysiology of these problems is not well-understood. In 38 children and young adults, we tested if these health problems were related to dysautonomia in an active standing test (Group 1: 19 patients after COVID-19; Group 2: 12 patients with a breakthrough infection despite a vaccination; and Group 3: 7 patients after a vaccination without COVID-19). The data were compared with a control group of 47 healthy age-matched patients, as recently published. All patients had a normal left ventricular function as measured by echocardiography. Significantly elevated diastolic blood pressure in all patient groups indicated a regulatory cardiovascular problem. Compared with the healthy control group, the patient groups showed significantly elevated heart rates whilst lying and standing, with significantly higher heart rate increases. The stress index was significantly enhanced in all patient groups whilst lying and standing. Significantly decreased pNN20 values, mostly whilst standing, indicated a lower vagus activity in all patient groups. The respiratory rates were significantly elevated in Groups 1 and 2. The uniform increase in the heart rates and stress indices, together with low pNN20 values, indicated dysautonomia in children with health problems after COVID-19 disease and/or vaccination. A total of 8 patients fulfilled the criteria of postural orthostatic tachycardia syndrome and 9 patients of an inappropriate sinus tachycardia, who were successfully treated with omega-3 fatty acid supplementation and pharmacotherapy.